Cytomegalovirus microRNAs Facilitate Persistent Virus Infection in Salivary Glands
Lars Dölken,Astrid Krmpotić,Sheila Kothe,Lee Tuddenham,Mélanie Tanguy,Lisa Marcinowski,Zsolt Ruzsics,Naama Elefant,Yael Altuvia,Hanah Margalit,Ulrich H. Koszinowski,Stipan Jonjić,Sébastien Pfeffer +12 more
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TLDR
During subacute infection of a mutant mouse cytomegalovirus lacking two viral miRNAs, virus production is selectively reduced in salivary glands, an organ essential for virus persistence and horizontal transmission, pointing towards a miRNA-based immunoevasion mechanism important for long-term virus persistence.Abstract:
Micro (mi)RNAs are small non-coding RNAs that regulate the expression of their targets' messenger RNAs through both translational inhibition and regulation of target RNA stability. Recently, a number of viruses, particularly of the herpesvirus family, have been shown to express their own miRNAs to control both viral and cellular transcripts. Although some targets of viral miRNAs are known, their function in a physiologically relevant infection remains to be elucidated. As such, no in vivo phenotype of a viral miRNA knock-out mutant has been described so far. Here, we report on the first functional phenotype of a miRNA knock-out virus in vivo. During subacute infection of a mutant mouse cytomegalovirus lacking two viral miRNAs, virus production is selectively reduced in salivary glands, an organ essential for virus persistence and horizontal transmission. This phenotype depends on several parameters including viral load and mouse genetic background, and is abolished by combined but not single depletion of natural killer (NK) and CD4+ T cells. Together, our results point towards a miRNA-based immunoevasion mechanism important for long-term virus persistence.read more
Citations
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Journal ArticleDOI
Virus-encoded microRNAs
TL;DR: It is hypothesized that many viral miRNAs may have evolved to regulate viral-encoded transcripts or networks of host genes that are unique to viral mi RNAs, including a likely abundant class of viralMiRNAs that may regulate only one or a few principal host genes.
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Virus-Encoded microRNAs: An Overview and a Look to the Future
TL;DR: New in vivo models that recapitulate persistent infections associated with viral pathogens are required and new ways of interacting with the host miRNA machinery including noncanonical miRNA biogenesis and new mechanisms of posttranscriptional cis gene regulation are revealed.
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MicroRNAs as mediators of viral evasion of the immune system.
TL;DR: This Review provides an overview of the present knowledge of the complex interactions of viruses with the microRNA machinery of cells.
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Viruses and microRNAs: RISCy interactions with serious consequences
TL;DR: The current understanding of how viral miRNAs influence viral replication and pathogenesis is reviewed and how viruses reshape the pattern of cellular miRNA expression is discussed.
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Degradation of cellular mir-27 by a novel, highly abundant viral transcript is important for efficient virus replication in vivo.
Lisa Marcinowski,Mélanie Tanguy,Astrid Krmpotić,Bernd Rädle,Vanda Juranić Lisnić,Lee Tuddenham,Béatrice Chane-Woon-Ming,Zsolt Ruzsics,Florian Erhard,Corinna Benkartek,Marina Babić,Ralf Zimmer,Joanne Trgovcich,Ulrich H. Koszinowski,Stipan Jonjić,Sébastien Pfeffer,Lars Dölken,Lars Dölken +17 more
TL;DR: Three mutant viruses no longer able to target miR-27a/b, either due to miRNA target site disruption or target site replacement, showed significant attenuation in multiple organs as early as 4 days post infection, indicating that degradation of miR/b is important for efficient MCMV replication in vivo.
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